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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules
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Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules

机译:青春期前人类精原细胞和小鼠性腺细胞共享种系干细胞调节分子的保守基因表达

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摘要

In the human testis, beginning at ≈2 months of age, gonocytes are replaced by adult dark (Ad) and pale (Ap) spermatogonia that make up the spermatogonial stem cell (SSC) pool. In mice, the SSC pool arises from gonocytes ≈6 days after birth. During puberty in both species, complete spermatogenesis is established by cells that differentiate from SSCs. Essentially pure populations of prepubertal human spermatogonia and mouse gonocytes were selected from testis biopsies and validated by confirming the presence of specific marker proteins in cells. Stem cell potential of germ cells was demonstrated by transplantation to mouse testes, following which the cells migrated to the basement membrane of the seminiferous tubule and were maintained similar to SSCs. Differential gene expression profiles generated between germ cells and testis somatic cells demonstrated that expression of genes previously identified as SSC and spermatogonial-specific markers (e.g., zinc-finger and BTB-domain containing 16, ZBTB16) was greatly elevated in both human spermatogonia and mouse gonocytes compared to somatic cells. Several genes were expressed at significantly higher levels in germ cells of both species. Most importantly, genes known to be essential for mouse SSC self-renewal (e.g., Ret proto-oncogene, Ret; GDNF-family receptor α1, Gfrα1; and B-cell CLL/lymphoma 6, member B, Bd6b) were more highly expressed in both prepubertal human spermatogonia and mouse gonocytes than in somatic cells. The results indicate remarkable conservation of gene expression, notably for self-renewal genes, in these prepubertal germline cells between two species that diverged phylogenetically ≈75 million years ago.
机译:在人的睾丸中,从大约2个月大开始,成年的暗色(Ad)和淡色(Ap)精原细胞取代了精子细胞,这些精原细胞组成了精原干细胞(SSC)库。在小鼠中,SSC集合来自出生后约6天的生殖细胞。在这两个物种的青春期,完全的精子形成是由与SSC分化的细胞建立的。从睾丸活检组织中选择基本纯净的青春期前人类精原细胞和小鼠性腺细胞群,并通过确认细胞中特定标记蛋白的存在进行验证。通过移植到小鼠睾丸证明了生殖细胞的干细胞潜能,此后细胞迁移到了生精小管的基底膜,并与SSCs保持相似。生殖细胞和睾丸体细胞之间产生的差异基因表达谱表明,先前鉴定为SSC和精原细胞特异性标记的基因(例如,锌指和含16个BTB结构域的ZTBB16)的表达在人类精原细胞和小鼠中均大大提高生殖细胞与体细胞相比。两种基因在两个物种的生殖细胞中均以明显更高的水平表达。最重要的是,已知对小鼠SSC自我更新至关重要的基因(例如,Ret原癌基因,Ret; GDNF家族受体α1,Gfrα1;以及B细胞CLL /淋巴瘤6,成员B,Bd6b)的表达更高。在青春期前的人类精原细胞和小鼠的性腺细胞中均比体细胞中的高。结果表明,在大约7500万年前发生了系统发育差异的两个物种之间的这些青春期前种系细胞中,基因表达特别是自我更新基因的表达得到了显着保护。

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  • 作者单位

    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;

    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;

    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;

    Penn Bioinformatics Core, University of Pennsylvania, Philadelphia, PA 19104;

    Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104;

    Department of Urology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104;

    Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104;

    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    mouse spermatogonia; spermatogenesis;

    机译:小鼠精原细胞精子发生;

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